Fibrinogens are cleaved by thrombin to yield fibrins, which polymerize to form the insoluble fibrin clot which blocks sites of vascular injury, preventing further blood loss. The clot is subsequently degraded by plasmin (fibrinolysis) []. There are three fibrinogens, alpha, beta and gamma []. Thrombin activates fibrinogen to release a fibrinopeptide []. The newly exposed N terminus forms an Glu-Lys isopeptide bond, which is stabilized by factor XIIIA []. Fibrinogen is also required for successful pregnancy, and in knockout mice fatal uterine bleeding occurs around the tenth day of gestation [].This entry represents the gamma chain of fibrinogen (FGG). Although a component of the fibrin clot, FGG is not a requirement for clot formation. FGG is not cleaved by thrombin, and no fibrinopeptide is released []. FGG carries the main binding site for the platelet receptor [].
Coronavirus encodes two viroporins, E protein and protein 3a, which act as ion-conductive pores in planar lipid bilayers and are required for maximal SARS-CoV replication and virulence []. In betacoronavirus, this protein plays a role in viral egress via lysosomal trafficking [, ]. Protein 3a from SARS-CoV-2 also blocks autolysosomes formation by binding and sequestering the host component VPS39 for homotypic fusion and protein sorting (HOPS) on late endosomes. This prevents fusion of autophagosomes with lysosomes, disrupting autophagy and facilitating virus egress [].This entry represents protein 3a encoded by Orf3/3a, also known as X1, which forms homotetrameric potassium, sodium or calcium sensitive ion channels (viroporin) and may modulate virus release. It has also been shown to up-regulate expression of fibrinogen subunits FGA, FGBand FGG in host lung epithelial cells [, , , ].3a protein is a pro-apoptosis-inducing protein. It localises to the endoplasmic reticulum (ER)-Golgi compartment. SARS-CoV causes apoptosis of infected cells through NLRP3 inflammasome activation, as ORF3a is a potent activator of the signals required for this activation, pro-IL-1beta gene transcription and protein maturation. This protein also promotes the ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) mediated by its interaction with TNF receptor-associated factor 3 (TRAF3). The expression of ORF3a induces NF-kappa B activation and up-regulates fibrinogen secretion with the consequent high cytokine production [, , , ]. Another apoptosis mechanism described for this protein is the activation of the PERK pathway of unfolded protein response (UPR), which causes phosphorylation of eIF2alpha and leads to reduced translation of cellular proteins as well as the activation of pro-apoptotic downstream effectors (i.e ATF4, CHOP) [].
